For many years, multiple myeloma was a death sentence, but new drug combinations and other advances have brought tremendous hope for patients. Now, in a study published in The Lancet Haematology, researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and Memorial Sloan Kettering Cancer Center have shown maintenance therapy with the drug lenalidomide arrests disease progression in many patients for extended periods.
“This study documents, for the first time, that patients with multiple myeloma can be free from detectable disease [minimal residual disease or MRD negative] for more than 10 years,” said C. Ola Landgren, M.D., professor of medicine and chief of the Myeloma Program. “That’s just mind-blowing for me. When I started treating patients with multiple myeloma, one to three years of overall survival was the norm.”
Though lenalidomide has been used as a multiple myeloma maintenance therapy for years, no one had studied its long-term impact on the dynamics of MRD status and how it translates into patient survival. This phase 2 study fills that gap and provides good news for patients and clinicians.
Combination therapy results
The trial enrolled 108 newly diagnosed multiple myeloma patients and followed them for several years. After five years, progression-free survival was 64%. The study also found that patients who received combination therapy did as well as those who received high-dose chemotherapy and stem cell transplants — a far more arduous and risky approach.
The paper also offers great potential to guide patient care. Patients who showed sustained MRD negativity for more than a year had better outcomes. On the other hand, those who started MRD negative but became MRD positive within a year had a much higher risk of disease progression.
Importantly, patients who never reached MRD negativity, but remained low-level MRD positive, showed were often free from disease progression for long periods.
“Some of these patients were not MRD negative, but they were just barely positive,” Dr. Landgren said. “But they stayed on maintenance, and were followed for many years, and their progression-free survival remained intact. Their disease burden did not increase.” Understanding these dynamics can help oncologists design more personalized treatment plans.
Indications for future care
The authors believe this extended progression-free survival for so many patients, even when they received less aggressive treatments, combined with disease markers that can show which patients are at higher risk for progression, bodes well for the future of multiple myeloma care.
A follow-up study is already being conducted by the study team. Using single-cell sequencing and other advanced methods, they are examining the underlying biological mechanisms that drive the clinical observations in the current study.
“We are breaking new ground in our understanding of the long-term sustained freedom from disease toward a cure,” Dr. Landgren said.